The 2006 discovery that mature skin cells can be converted into stem cells opened up exciting possibilities in regenerative medicine. Now almost a decade later, the Nobel-Prize winning research of Shinya Yamanaka is still opening doors for scientists across different arms of medical research. In what it labels as a first, a team from the University of North Carolina at Chapel Hill (UNC) has built on this technology to transform adult skin cells into cancer-killing stem cells that seek and destroy brain tumors.

Glioblastomas are the most common and fatal form of brain cancer, carrying a survival rate beyond two years of just 30 percent. While surgeons can remove the tumor, often its cancerous tentacles take root deep in the brain and allow it to grow back. Most patients die within a year and a half of diagnosis.

Radiation and chemotherapy can be used to tackle tumors that cannot be surgically removed, but the UNC research team is working towards yet another treatment that zeroes in on these tentacles as a means of further boosting survival rates.

The team harvested adult skin cells called fibroblasts, which produce collagen and connective tissue, and engineered these to become induced neural stems cells. They then administered these cells to mice, observing that they had the ability to go hunting through the brain for remaining cancer cells and kill them off.

This led to an increase in survival times ranging from 160 to 220 percent, depending on the type of tumor. The team says it is also possible to engineer the stem cells to produce a tumor-killing protein, which would make them an even more potent weapon against cancer.

The team mixed stem cells into an FDA-approved surgical glue, which provided a physical matrix to support them while they sought out the cancerous tentacles. The team is now exploring ways to further improve this staying power, along with the potential to load anti-cancer drugs into the stem cells.

“Our work represents the newest evolution of the stem-cell technology that won the Nobel Prize in 2012,” says Shawn Hingtgen, an assistant professor at UNC. “We wanted to find out if these induced neural stem cells would home in on cancer cells and whether they could be used to deliver a therapeutic agent. This is the first time this direct reprogramming technology has been used to treat cancer.”

Scientists have reversed the aging process in human adult stem cells, which are in turn responsible for replacing aged cells throughout the body (Image: Public Library of Science)

By now, most people are probably aware of the therapeutic value of stem cells, as they can become any other type of cell in the human body. One of their main duties, in fact, is to replace those other cells as they degrade. Once people reach an advanced age, however, even the stem cells themselves start to get old and nonfunctional – when the cells that are supposed to replace the other cells can’t do their job anymore, age-related tissue problems start occurring. A team of researchers from the Buck Institute for Research on Aging in collaboration with the Georgia Institute of Technology, however, may be on the way to solving that problem. They have succeeded in reversing the aging process in human adult stem cells.

When regular cells become aged, the caps on the end of their chromosomes (known as telomeres) get shorter. It is therefore hypothesized that many age-related problems are due to the shortening of these telomeres. Given that adult stem cells retain their full telomeres, however, the scientists had to find some other discernible way in which they age.

To do so, they compared the DNA of freshly-isolated adult stem cells from young donors, with that of stem cells from the same donors, but that had undergone an accelerated aging process in the lab. It turned out that most of the DNA damage in the older cells was due to the activity of parts of the cell genome known as retrotransposons. While young cells are able to limit this activity and deal with the damage it causes, older cells are not.

By suppressing the “accumulation of toxic transcripts” from the retrotransposons, however, the researchers were able to reverse the aging process in the older stem cells. They were, in fact, even able to regress them to an earlier stage of development.

The Buck Institute/Georgia Tech team is now looking at how suitable the rejuvenated stem cells may be for treating degenerative disorders such as arthritis, osteoporosis and metabolic syndromes.

A paper on the research was recently published in the journal Cell Cycle.

As one of the follically-challenged, any new breakthroughs in the area of hair regeneration will generally get my attention. When stem cells first started to gain widespread media attention I, no doubt like many others, thought a full head of hair was just around the corner. But despite numerous developments, years later my dome is still of the chrome variety. Providing the latest cause for cautious optimism, researchers have now developed a way to generate a large number number of hair-follicle-generating stem cells from adult cells.

In what they claim is a world first, researchers from the University of Pennsylvania (UPenn) and the New Jersey Institute of Technology have developed a technique to convert adult human stem cells into epithelial stem cells (EpSCs).

By adding three genes to human skin cells called dermal fibroblasts that live in the dermis layer of the skin and generate connective tissue, a team led by Xiaowei “George” Xu, MD, PhD, at the Perelman School of Medicine was able to convert them into induced pluripotent stem cells (iPSCs). The iPSCs, which have the ability to differentiate into any cell type, were then converted into epithelial stem cells (EpSCs) that are normally found at the bulge of hair follicles.

Through careful control of the timing of delivery of growth factors to the cells, the researchers say they were able to turn over 25 percent of the iPSCs into EpSCs in 18 days. When they then mixed these EpSCs with mouse follicular inductive dermal cells and grafted them onto the skin of immunodeficient mice, functional human epidermis and follicles similar to hair follicles were produced.

“This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles,” said Xu, who added that these cells have many potential applications, including wound healing, cosmetics, and hair regeneration.

But some hurdles still need to be jumped before I make my first trip to the hairdresser in a decade. Xu points out that when a person loses hair, they lose not only epithelial cells, but also a kind of adult stem cell called dermal papillae. “We have solved one major problem, the epithelial component of the hair follicle. We need to figure out a way to also make new dermal papillae cells, and no one has figured that part out yet.”

On a positive note, researchers from the Tokyo University of Science have reported promising results in reconstructing hair follicle germs from adult epithelial stem cells and cultured dermal papilla cells, so even though we haven’t rounded the corner yet,it definitely seems to be getting closer.

NASAL CELL MATERIAL USED TO GET A MAN WALKING AGAIN AFTER DEBILITATING SPINAL INJURIES

FIRST STEPS: Darek Fidyka walks with the aid of leg-braces and a walking frame at the Akron Neuro-Rehabilitation Center in Wroclaw, Poland. Photo: AFP

A paralysed man has begun to walk again after pioneering surgery injected cells from his nasal cavity into his spine. How was this possible – and what does it mean for others with spinal injury? Kate Hagan stitches together the evidence.

Darek Fidyka sounds as though he has been through a lot. How did he lose his ability to walk?

A Bulgarian firefighter, Mr Fidyka’s spinal cord was severed after he was repeatedly stabbed in the back during a knife attack in 2010. It left the 40-year-old paralysed from the chest down. Despite two years of intensive physiotherapy he had showed no sign of recovery.

Why did scientists think he might be able to walk again?

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Scientists have long recognised the potential of particular cells in the olfactory bulb, at the top of the nasal cavity, to stimulate growth of nerve fibres. Called olfactory ensheathing cells, they act as pathway cells to enable nerve fibres in the olfactory system to be constantly renewed throughout a person’s life, preserving the senses of smell and taste.

The role of the cells in the olfactory bulb has led scientists to explore their potential in the spinal cord, where regeneration of nerve fibres fails after spinal injury.

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Mr Fidyka had two operations. In the first, Polish surgeons removed one of his olfactory bulbs and grew the olfactory cells in culture in a laboratory. Two weeks later they injected the cells above and below Mr Fidyka’s spinal injury. They also transplanted nerve tissue from his ankle into his injured spinal cord to form a bridge for nerve fibres to grow.

How has the operation changed his life?

Three months after the treatment Mr Fidyka noticed that he was developing muscle on his left thigh. After six months, he took steps along parallel bars using leg braces. Two years later he can walk with a frame and drive a car. He has also recovered some bladder, bowel and sexual function.

Mr Fidyka said walking again was an incredible feeling. “When you can’t feel almost half your body, you are helpless, but when it starts coming back it’s like you were born again,” he told the BBC. Mr Fidyka says he tires quickly when walking, but believes it is realistic to believe he will one day become independent.

What does this mean for paralysed people – will this treatment be broadly applicable? In short, will they be able to walk again?

Researchers involved in Mr Fidyka’s case say the treatment will need to be successfully repeated to definitively show the approach can repair a severed spinal cord. They hope to treat another 10 patients over coming years and have said they will consider patients from anywhere in the world who would likely have a similar injury to Mr Fidyka.

Florey Institute head of spinal research Stephen Davies warned the treatment may not work for all types of spinal injury. He said it was “too early to claim that the experimental therapy represents a silver bullet” and a clinical trial with large numbers of patients was needed to determine its benefits.

And Griffith University group leader of olfactory and brain repair James St John said Mr Fidyka’s case had demonstrated that transplanting olfactory cells into the spinal cord could restore sensation and some motor control in humans – but stressed there was still a long way to go.

“Each patient’s injuries are different and we don’t yet understand why there is recovery in some situations but not in others,” Dr St John said. “It is also important to understand that there are many types of olfactory [cells] and the correct combination of cells has not yet been determined.”

Does the scientific community have any reservations about what appears to be groundbreaking research?

The response has generally been: it is very early days for this form of treatment; let’s not get ahead of ourselves; expect mixed results as further trials are run.

Simone Di Giovanni, the chair in restorative neuroscience at Imperial College London, is among those urging caution about raising false hope for patients with spinal cord injury.

“One case of a patient improving neurological impairment after spinal cord knife injury following nerve and olfactory cell transplantation is simply anecdotal and cannot represent any solid scientific evidence to elaborate on. In fact there is no evidence that the transplant is responsible for the reported neurological improvement,” he said.

And Dusko Ilic, a senior lecturer in stem cell science at King’s College London, said transplantation of olfactory ensheathing cells in animal studies had varied results.

University of Nottingham professor of advanced drug delivery and tissue engineering Kevin Shakesheff added: “At best I’d expect to see quite a lot of variability in the clinical success because of the complexity of the tissue they are trying to repair and the different extent of damage in each patient.”

(Reuters) – Scientists have for the first time created a functional human liver from stem cells derived from skin and blood and say their success points to a future where much-needed livers and other transplant organs could be made in a laboratory.

While it may take another 10 years before lab-grown livers could be used to treat patients, the Japanese scientists say they now have important proof of concept that paves the way for more ambitious organ-growing experiments.

AAA

“The promise of an off-the-shelf liver seems much closer than one could hope even a year ago,” said Dusko Illic, a stem cell expert at King’s College London who was not directly involved in the research but praised its success.

He said however that while the technique looks “very promising” and represents a huge step forward, “there is much unknown and it will take years before it could be applied in regenerative medicine.”

Researchers around the world have been studying stem cells from various sources for more than a decade, hoping to capitalize on their ability to transform into a wide variety of other kinds of cell to treat a range of health conditions.

There are two main forms of stem cells – embryonic stem cells, which are harvested from embryos, and reprogrammed “induced pluripotent stem cells” (iPS cells), often taken from skin or blood.

AAA

Countries across the world have a critical shortage of donor organs for treating patients with liver, kidney, heart and other organ failure. Scientists are keenly aware of the need to find other ways of obtaining organs for transplant.

The Japanese team, based at the Yokohama City University Graduate School of Medicine in Japan, used iPS cells to make three different cell types that would normally combine in the natural formation of a human liver in a developing embryo – hepatic endoderm cells, mesenchymal stem cells and endothelial cells – and mixed them together to see if they would grow.

They found the cells did grow and began to form three-dimensional structures called “liver buds” – a collection of liver cells with the potential to develop into a full organ.

When they transplanted them into mice, the researchers found the human liver buds matured, the human blood vessels connected to the mouse host’s blood vessels and they began to perform many of the functions of mature human liver cells.

AAA

“To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells,” the researchers wrote in the journal Nature.

Malcolm Allison, a stem cell expert at Queen Mary University of London, who was not involved in the research, said the study’s results offered “the distinct possibility of being able to create mini livers from the skin cells of a patient dying of liver failure” and transplant them to boost the failing organ.

Takanori Takebe, who led the study, told a teleconference he was so encouraged by the success of this work that he plans similar research on other organs such as the pancreas and lungs.

A team of American researchers said in April they had created a rat kidney in a lab that was able to function like a natural one, but their method used a “scaffold” structure from a kidney to build a new organ.

And in May last year, British researchers said they had turned skin cells into beating heart tissue that might one day be able to be used to treat heart failure.

That livers and other organs may one day be made from iPS cells is an “exciting” prospect, said Matthew Smalley of Cardiff University’s European Cancer Stem Cell Research Institute.

Chris Mason, a regenerative medicine expert at University College London said the greatest impact of iPS cell-liver buds might be in their use in improving drug development.

“Presently to study the metabolism and toxicology of potential new drugs, human cadaveric liver cells are used, ” he said. “Unfortunately these are only available in very limited quantities”.

The suggestion from this new study is that mice transplanted with human iPS cell-liver buds might be used to test new drugs to see how the human liver would cope with them and whether they might have side-effects such as liver toxicity.

Reuters) – Scientists have for the first time created a functional human liver from stem cells derived from skin and blood and say their success points to a future where much-needed livers and other transplant organs could be made in a laboratory.

While it may take another 10 years before lab-grown livers could be used to treat patients, the Japanese scientists say they now have important proof of concept that paves the way for more ambitious organ-growing experiments.

“The promise of an off-the-shelf liver seems much closer than one could hope even a year ago,” said Dusko Illic, a stem cell expert at King’s College London who was not directly involved in the research but praised its success.

He said however that while the technique looks “very promising” and represents a huge step forward, “there is much unknown and it will take years before it could be applied in regenerative medicine.”

AAA

Researchers around the world have been studying stem cells from various sources for more than a decade, hoping to capitalize on their ability to transform into a wide variety of other kinds of cell to treat a range of health conditions.

There are two main forms of stem cells – embryonic stem cells, which are harvested from embryos, and reprogrammed “induced pluripotent stem cells” (iPS cells), often taken from skin or blood.

Countries across the world have a critical shortage of donor organs for treating patients with liver, kidney, heart and other organ failure. Scientists are keenly aware of the need to find other ways of obtaining organs for transplant.

The Japanese team, based at the Yokohama City University Graduate School of Medicine in Japan, used iPS cells to make three different cell types that would normally combine in the natural formation of a human liver in a developing embryo – hepatic endoderm cells, mesenchymal stem cells and endothelial cells – and mixed them together to see if they would grow.

They found the cells did grow and began to form three-dimensional structures called “liver buds” – a collection of liver cells with the potential to develop into a full organ.

When they transplanted them into mice, the researchers found the human liver buds matured, the human blood vessels connected to the mouse host’s blood vessels and they began to perform many of the functions of mature human liver cells.

AAA

“To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells,” the researchers wrote in the journal Nature.

Malcolm Allison, a stem cell expert at Queen Mary University of London, who was not involved in the research, said the study’s results offered “the distinct possibility of being able to create mini livers from the skin cells of a patient dying of liver failure” and transplant them to boost the failing organ.

Takanori Takebe, who led the study, told a teleconference he was so encouraged by the success of this work that he plans similar research on other organs such as the pancreas and lungs.

A team of American researchers said in April they had created a rat kidney in a lab that was able to function like a natural one, but their method used a “scaffold” structure from a kidney to build a new organ.

AAA

And in May last year, British researchers said they had turned skin cells into beating heart tissue that might one day be able to be used to treat heart failure.

That livers and other organs may one day be made from iPS cells is an “exciting” prospect, said Matthew Smalley of Cardiff University’s European Cancer Stem Cell Research Institute.

Chris Mason, a regenerative medicine expert at University College London said the greatest impact of iPS cell-liver buds might be in their use in improving drug development.

“Presently to study the metabolism and toxicology of potential new drugs, human cadaveric liver cells are used, ” he said. “Unfortunately these are only available in very limited quantities”.

The suggestion from this new study is that mice transplanted with human iPS cell-liver buds might be used to test new drugs to see how the human liver would cope with them and whether they might have side-effects such as liver toxicity.

EMBRYONIC stem cells have been used to treat human illness for the first time, improving the sight of two women with severe vision loss.

The controversial development could give hope to hundreds of thousands of people suffering macular degeneration – one of the most common forms of blindness in First World countries – and has been hailed a historic step by stem cell scientists.

In a US trial last year, two legally blind women reported sight improvements after receiving a small dose of embryonic stem cell transplantations in their eyes.

Both had different forms of macular degeneration, a group of diseases that affect the retina, causing loss of central vision.

After the transplant in July, the first woman, who suffers from dry age-related macular degeneration, went from being able to read 21 letters on a sight test chart to 28. The second woman, who has Stargardt’s disease, went from being unable to read any letters to reading five. While the scientists who conducted the study are cautious about the results, tests indicate that healthy cells have grown where the treatment was injected.

They said the patients had shown no negative reactions.

The study, reported in The Lancet this week, was led by Robert Lanza, the chief scientific officer at Advanced Cell Technology in the US – the stem cell company that funded the trial.

The research has taken place amid debate about whether the stem cells should be used because they are derived from five- to six-day-old human embryos.

The disease affects one in seven people over 50, the Macular Degeneration Foundation says.

Making blood from human skin

By Grant Banks

03:48 November 14, 2010

Blood transfusions may one day come from blood produced from a patient’s skin

A new technique that allows blood to be made directly from skin cells has been discovered. The pioneering approach by Canadian researchers uses human skin stem cells to create blood stem cells without an intermediate step that previously was thought necessary.

Until now to make blood stem cells, the building blocks for a variety human cells (called pluripotent stem cells) have been used as a steppingstone a process. This has proven largely inefficient, but research led by Mick Bhatia, scientific director ofMcMaster’s Stem Cell and Cancer Research Instituteat the Michael G DeGroote School of Medicine, has shown that making blood from skin can be achieved in a one step process.

Cynthia Dunbar, head of the molecular hematopoiesis at the U.S National Institutes of Health said: “Bhatia’s approach detours around the pluripotent stem cell stage and thus avoids many safety issues, increases efficiency, and also has the major benefit of producing adult-type l blood cells instead of fetal blood cells, a major advantage compared to the thus far disappointing attempts to produce blood cells from human embryonic stem cells or induced pluripotent stem cells.”

The discovery was replicated several times over two years using human skin from both the young and the elderly to prove it works for any age of person.

The approach could be used for creating blood for surgery or treating conditions like anemia from a patch of the patient’s skin. Other potential applications include generating bone marrow and improved treatment of leukaemia and other types of cancer, including solid tumors.

“We have shown this works using human skin. We know how it works and believe we can even improve on the process,” Bhatia said. “We’ll now go on to work on developing other types of human cell types from skin, as we already have encouraging evidence.”

“This finding will no doubt be met with excitement in the research and medical communities,” said Michael Rudnicki, director of The Stem Cell Network. “It’s been nearly 50 years since blood stem cells were first identified here in Canada and it’s fitting that this incredible new discovery should have happened here as well.”

Florida resident Naidelys Montoya is one of those taking advantage of the process.

The Hialeah woman didn’t wait for her son’s baby teeth to fall out but took the boy to an oral surgeon to have two of the loose ones extracted for their stem cells in case her son Raul Estrada, 6, might need them for a future illness, she says.

“I believe in this,” Montoya said. “I did as a precaution against things that could happen in the future.”

Many question the procedure.

It’s expensive, costing $590 upfront and $100 a year to store stem cells from up to four teeth for up to 20 years.

And it’s speculative, with the first FDA-approved practical use of such stem cells likely years away.

Still, supporters are confident in the worth of the process.

“I can’t help but feel excitement for their potential use in regenerating different tissues in the human body,” Dr. Jeremy Mao, director of the Regenerative Medicine Laboratory at Columbia University, said.

Mao also is chief science adviser to StemSave, a New York City company that freezes the stem cells and stores them for later use, the Herald reported.

The American Dental Association, while cautiously optimistic about the potential of dental stem cells, urges parents to consider both the cost and the rarity of use.

“That’s the question people have to ask themselves,” said Dr. Jeffrey Blum, the Miami Beach oral surgeon who pulled Raul Estrada’s teeth.

“Am I saving this for no reason? Is it worth what I’m paying? Essentially it’s an insurance policy.”